Abstract Association between alcohol intake and Coronavirus disease 2019 (COVID-19) risk has been explored in several observational studies, but the results are still controversial. These associations may be biased by reverse causation or confounded by other environmental exposures. To avoid potential biases, we used Mendelian randomization (MR) method to evaluate whether alcohol intake is the causal risk factor for COVID-19. Two-sample MR analyses were performed utilizing summary data from the UK Biobank with 38,984 COVID-19 patients and 1,644,784 control participants. Both inverse-variance weighted (IVW) and genetic risk score (GRS) methods were applied to estimate the relationship including COVID-19 vs. general population, hospitalized COVID-19 vs. not hospitalized COVID-19, hospitalized COVID-19 vs. general population, and severe COVID-19 vs. general population. Additionally, we conducted various sensitivity analyses to evaluate the impact of assumptions on the findings and ensure the robustness of the results. Using 80 single nucleotide polymorphisms as instrumental variables, we found that alcohol intake was not significantly associated with the occurrence of COVID-19 in both IVW and GRS methods (IVW: beta = 0.0372; 95% CI − 0.1817 to 0.2561; P = 0.74; GRS: beta = 0.0372, 95% CI − 0.1737 to 0.2481, P = 0.73). Furthermore, similar results were also observed in comparison hospitalized COVID-19 with not hospitalized COVID-19 (IVW: beta = − 0.3625; 95% CI − 1.4151 to 0.6900; P = 0.50; GRS: beta = − 0.3625, 95% CI − 1.3633 to 0.6383, P = 0.48), hospitalized COVID-19 with general population (IVW: beta = − 0.1203; 95% CI − 0.5997 to 0.3591; P = 0.62; GRS: beta = − 0.1203, 95% CI − 0.5352 to 0.2946, P = 0.57), and severe COVID-19 with general population (IVW: beta = 0.2963; 95% CI − 0.3682 to 0.9607; P = 0.38; GRS: beta = 0.2963, 95% CI − 0.3240 to 0.9166, P = 0.35). Besides, the heterogeneity and sensitivity tests suggested absence of bias due to pleiotropy. Our results highlight no evidence to support the causal role of alcohol consumption in COVID-19 risk. Further large-scale prospective studies are warranted to replicate our findings.
Chronic hepatitis B virus (HBV) infection can significantly increase the incidence of cirrhosis and liver cancer, and there is no curative treatment. The persistence of HBV covalently closed circular DNA (cccDNA) is the major obstacle of antiviral treatments. cccDNA is formed through repairing viral partially double-stranded relaxed circular DNA (rcDNA) by varies host factors. However, the detailed mechanisms are not well characterized. To dissect the biogenesis of cccDNA, we took advantage of an in vitro rcDNA repair system to precipitate host factors interacting with rcDNA and identified co-precipitated proteins by mass spectrometry. Results revealed the MRE11–RAD50–NBS1 (MRN) complex as a potential factor. Transiently or stably knockdown of MRE11, RAD50 or NBS1 in hepatocytes before HBV infection significantly decreased viral markers, including cccDNA, while reconstitution reversed the effect. Chromatin immunoprecipitation assay further validated the interaction of MRN complex and HBV DNA. However, MRN knockdown after HBV infection showed no effect on viral replication, which indicated that MRN complex inhibited the formation of cccDNA without affecting its stability or transcriptional activity. Interestingly, Mirin, a MRN complex inhibitor which can inhibit the exonuclease activity of MRE11 and MRN-dependent activation of ATM, but not ATM kinase inhibitor KU55933, could decrease cccDNA level. Likewise, the MRE11 endonuclease activity inhibitor PFM01 treatment decreased cccDNA. MRE11 nuclease assays indicated that rcDNA is a substrate of MRE11. Furthermore, the inhibition of ATR-CHK1 pathway, which is known to be involved in cccDNA formation, impaired the effect of MRN complex on cccDNA. Similarly, inhibition of MRE11 endonuclease activity mitigated the effect of ATR-CHK1 pathway on cccDNA. These findings indicate that MRN complex cooperates with ATR-CHK1 pathway to regulate the formation of HBV cccDNA. In summary, we identified host factors, specifically the MRN complex, regulating cccDNA formation during HBV infection. These findings provide insights into how HBV hijacks host enzymes to establish chronic infection and reveal new therapeutic opportunities.
Dysphagia is common in elderly patients with dementia and is one of the common clinical geriatric syndromes. It imposes a heavy burden on patients and their caregivers and is becoming an important public health problem. This study examined the association between dysphagia in older dementia patients in the ICU and the subsequent adverse health outcomes they experience.A retrospective analysis of adults (≥65 years) with dementia in ICUs of a Boston tertiary academic medical center was conducted. Using the International Classification of Diseases' Ninth and Tenth Revisions, dementia patients were identified. The study cohort comprised 1009 patients, median age 84.82 years, 56.6% female, predominantly White (72.9%). Patients were grouped based on swallowing function: dysphagia (n=282) and no-dysphagia (n=727). Dysphagia was identified via positive bedside swallowing screening. Primary outcomes were 90- and 180-day mortality, secondary outcomes included aspiration pneumonia, pressure injury, and delirium. Cohort characteristics were compared using the Wilcoxon rank-sum and chi-square tests. Dysphagia and outcomes correlations were examined via Kaplan-Meier survival analysis, Cox proportional-hazards regression models, logistic regression models, and subgroup analysis.After adjusting for covariates, the results from multivariate Cox proportional-hazards regression indicated that dysphagia was significantly associated with increased 90-day (HR=1.36, 95% CI=1.07-1.73, E-value=1.78) and 180-day (HR=1.47, 95% CI=1.18-1.82, E-value=1.94) mortality; the multifactorial logistic regression results indicated that dysphagia was associated with significant increases in pressure injury (OR=1.58, 95% CI=1.11-2.23, E-value=1.83) and aspiration pneumonia occurrence (OR=4.04, 95% CI=2.72-6.01, E-value=7.54), but was not significantly associated with delirium prevalence (OR=1.27, 95% CI=0.93-1.74).Dysphagia is likely to increase the risk of adverse health outcomes in older adults with dementia in ICU, and these adverse outcomes mostly include 90- and 180-day mortality, aspiration pneumonia, and pressure injury.
Abstract Background Since SCD ( plus ) was standardized, little is known about its demographic characteristics and its outcomes of neuropsychological assessments, including the SCD questionnaire 9 (SCD‐Q9). Objective To characterize SCD ( plus ) by comparing the neuropsychological features among its subgroups and with normal controls (NC). Also, to explore its demographics and to understand the relation of the chief complaints and the scores of SCD‐Q9. Methods Multistage stratified cluster random sampling was conducted to select participants. As a result, 84 NC and 517 SCD ( plus ) were included. SCD ( plus ) was further classified into several subgroups (SCD‐C: concerned cognitive decline; SCD‐F: complaints about SCD within the past five years; SCD‐P: feeling performance being not as good as their peers; SCD+: presented> 3 of SCD ( plus ) features; SCD‐: presented ≤ 3 of SCD ( plus ) features (see the diagnostic criteria for the details)) and between‐group comparisons of neuropsychological scores were conducted. Point‐biserial correlation and binary logistic regression analyses were performed to investigate the demographic characteristics of its subgroups. Finally, Spearman correlation was used to better understand the relation of SCD ( plus ) to SCD‐Q9. Results (1) Scores of AVLT‐LR (AVLT‐LR: Auditory Verbal Learning Test‐Long Delayed Recall) and MoCA‐B (MoCA: Montreal Cognitive Assessment‐Basic) were lower in the SCD‐P group than those in the NC group, and the SCD+ group scored lower in the MoCA‐B and CDT(CDT: Clock Drawing Test) than the SCD‐ group. (2) Females were more concerned than male participants. Individuals with lower education level felt that their cognitive performance were worse than their peers. Also, younger people might express concerns more than the more elderly. People who had complaints of SCD‐P might be more likely to report SCD‐C, but less likely to report SCD‐F. (3) Positive correlations were found between the chief complaints of SCD ( plus ) and some items of SCD‐Q9. Conclusions SCD ( plus ) may be related to demographic factors. Individuals with SCD ( plus ) already exhibited cognitive impairment, which can be detected by SCD‐Q9.
Introduction: Liver cirrhosis is caused by the development of various acute and chronic liver diseases. Esophageal varices is a common and serious complication of liver cirrhosis during decompensation. Despite the development of various treatments, the prognosis for liver cirrhosis with esophageal varices (LCEV) remains poor. We aimed to establish and validate a nomogram for predicting in-hospital death in LCEV patients. Methods: Data on LCEV patients were extracted from the Medical Information Mart for Intensive Care III and IV (MIMIC-III and MIMIC-IV) database. The patients from MIMIC-III were randomly divided into training and validation cohorts. Training cohort was used for establishing the model, validation and MIMIC-IV cohorts were used for validation. The independent prognostic factors for LCEV patients were determined using the least absolute shrinkage and selection operator (LASSO) method and forward stepwise logistic regression. We then constructed a nomogram to predict the in-hospital death of LCEV patients. Multiple indicators were used to validate the nomogram, including the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow test, integrated discrimination improvement (IDI), net reclassification index (NRI), and decision curve analysis (DCA). Results: Nine independent prognostic factors were identified by using LASSO and stepwise regressions: age, Elixhauser score, anion gap, sodium, albumin, bilirubin, international normalized ratio, vasopressor use, and bleeding. The nomogram was then constructed and validated. The AUC value of the nomogram was 0.867 (95% CI = 0.832-0.904) in the training cohort, 0.846 (95% CI = 0.790-0.896) in the validation cohort and 0.840 (95% CI = 0.807-0.872) in the MIMIC-IV cohort. High AUC values indicated the good discriminative ability of the nomogram, while the calibration curves and the Hosmer-Lemeshow test results demonstrated that the nomogram was well-calibrated. Improvements in NRI and IDI values suggested that our nomogram was superior to MELD-Na, CAGIB, and OASIS scoring system. DCA curves indicated that the nomogram had good value in clinical applications. Conclusion: We have established the first prognostic nomogram for predicting the in-hospital death of LCEV patients. The nomogram is easy to use, performs well, and can be used to guide clinical practice, but further external prospective validation is still required.
Background: Diabetes mellitus (DM) has a high morbidity and mortality worldwide, and it is a risk factor for cardiovascular diseases. Non-diabetic stress hyperglycemia is common in severely ill patients, and it could affect prognosis. This study aimed to analyze the influence of different blood glucose levels on prognosis from the perspective of stress hyperglycemia by comparing them with normal blood glucose levels and those of patients with DM. Methods: A retrospective study of 1,401 patients in coronary care unit (CCU) from the critical care database called Medical Information Mart for Intensive Care IV was performed. Patients were assigned to the following groups 1–4 based on their history of DM, random blood glucose, and HbA1c levels: normal blood glucose group, moderate stress hyperglycemia group, severe stress hyperglycemia group and DM group. The main outcome of this study was 30- and 90-day mortality rates. The associations between groups and outcomes were analyzed using Kaplan–Meier survival analysis, Cox proportional hazard regression model and competing risk regression model. Results: A total of 1,401 patients in CCU were enrolled in this study. The Kaplan–Meier survival curve showed that group 1 had a higher survival probability than groups 3 and 4 in terms of 30- and 90-day mortalities. After controlling the potential confounders in Cox regression, groups 3 and 4 had a statistically significant higher risk of both mortalities than group 1, while no difference in mortality risk was found between groups 2 and 1. The hazard ratios [95% confidence interval (CI)] of 30- and 90-day mortality rates for group 3 were 2.77(1.39,5.54) and 2.59(1.31,5.12), respectively, while those for group 4 were 1.92(1.08,3.40) and 1.94(1.11,3.37), respectively. Conclusions: Severe stress hyperglycemia (≥200 mg/dL) in patients without DM in CCU may increase the risk of short-term death, which is greater than the prognostic effect in patients with diabetes. Patients with normal blood glucose levels and moderate stress hyperglycemia (140 mg/dL ≤ RBG <200 mg/dL) had no effect on short-term outcomes in patients with CCU.
Abstract Background Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. Methods A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. Results The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07–2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). Conclusion ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.
Lung infection is a common cause of sepsis, and patients with sepsis and lung infection are more ill and have a higher mortality rate than sepsis patients without lung infection. We constructed a nomogram prediction model to accurately evaluate the prognosis of and provide treatment advice for patients with sepsis and lung infection.Data were retrospectively extracted from the Medical Information Mart for Intensive Care (MIMIC-III) open-source clinical database. The definition of Sepsis 3.0 [10] was used, which includes patients with life-threatening organ dysfunction caused by an uncontrolled host response to infection, and SOFA score ≥ 2. The nomogram prediction model was constructed from the training set using logistic regression analysis, and was then internally validated and underwent sensitivity analysis.The risk factors of age, lactate, temperature, oxygenation index, BUN, lactate, Glasgow Coma Score (GCS), liver disease, cancer, organ transplantation, Troponin T(TnT), neutrophil-to-lymphocyte ratio (NLR), and CRRT, MV, and vasopressor use were included in the nomogram. We compared our nomogram with the Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score II (SAPSII), the nomogram had better discrimination ability, with areas under the receiver operating characteristic curve (AUROC) of 0.743 (95% C.I.: 0.713-0.773) and 0.746 (95% C.I.: 0.699-0.790) in the training and validation sets, respectively. The calibration plot indicated that the nomogram was adequate for predicting the in-hospital mortality risk in both sets. The decision-curve analysis (DCA) of the nomogram revealed that it provided net benefits for clinical use over using the SOFA score and SAPSII in both sets.Our new nomogram is a convenient tool for accurate predictions of in-hospital mortality among ICU patients with sepsis and lung infection. Treatment strategies that improve the factors considered relevant in the model could increase in-hospital survival for these ICU patients.
Objective
To assess the correlation of CHADS2 and CHA2DS2-VASc scores for short-term prognosis in acute ischemic stroke patients with nonvalvular atrial fibrillation.
Methods
Consecutive ischemic stroke patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after stroke were registered and 206 patients with nonvalvular atrial fibrillation were enrolled in this study. Patients were divided into 3 groups on the basis of CHADS2 scores (0, 1, 2 to 6) and CHA2DS2-VASc score (0, 1, 2 to 9). And recovery was assessed by modified Rankin Scale (mRS) at 3 months follow-up (mRS≤2 reflected good prognosis and mRS≥5 implicated unfavorable outcome). After screening the risk factors affecting prognosis using univariate analysis, the correlation of CHADS2 and CHA2DS2-VASc scores for short-term prognosis was estimated using Logistic regression model.
Results
The proportion of high-risk group was significantly higher (P<0.01) while that of low-risk group significantly lower as stratified by CHA2DS2-VASc score than by CHADS2 scores (P<0.01). Logistic regression model results suggested that CHA2DS2-VASc score was an independent predictor of good prognosis and unfavorable outcome. CHADS2≥2, and CHA2DS2-VASc≥2 were all correlated with prognosis, but multivariate logistic analysis identified only CHA2DS2-VASc≥2 as the independent risk factor for prognosis (OR=3.24, 95%CI: 1.32-6.98, P=0.00).
Conclusions
The average score of CHA2DS2-VASc is higher than that of CHADS2 and has better predictive ability for prognosis in acute ischemic stroke patients with nonvalvular atrial fibrillation.
Key words:
Atrial fibrillation; Stroke; CHADS2 score; CHA2DS2-VASc score; Aged
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